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Localizzazione cellulare e sinpatica di GAT-1 e GAT-3 nella corteccia cerebrale di ratto
Nel presente lavoro è stata finemente studiata la distribuzione e la localizzazione
dei trasportatori del GABA, GAT-1 e GAT-3 nella corteccia cerebrale di ratto, al fine di
estendere le attuali conoscenze riguardo la loro espressione. A tale scopo sono stati
studiati sistematicamente la distribuzione sub-cellulare, l’organizzazione sinaptica e i
livelli sinaptici di GAT-1 e GAT-3 nella corteccia cerebrale mediante microscopia
elettronica con tecniche di pre- e post-embedding e microscopia confocale
tridimensionale ad alta risoluzione.
In generale gli studi di pre-embedding hanno permesso di evidenziare una
complessa localizzazione di entrambi i trasportatori GAT-1 e GAT-3. Sebbene GAT-1
sia principalmente neuronale, è largamente espresso anche nei processi gliali, mentre
GAT-3 è prevalentemente gliale e solo una piccola frazione è presente anche nei
neuroni. L’espressione di GAT-1, e non di GAT-3, è polarizzata nelle sinapsi corticali.
A livello sinaptico, GAT-1 è prevalentemente espresso nei terminali assonici di sinapsi
simmetriche compresi diversi processi gliali, seppure una frazione non trascurabile di
GAT-1 sia presente anche a livello di sinapsi asimmetriche (nei processi gliali
perisinaptici e dendriti postsinaptici). Al contrario GAT-3, a livello sinaptico, è
maggiormente espresso nei processi perisinaptici ed è equamente distribuito tra sinapsi
simmetriche e asimmetriche.
Gli studi di post-embedding dimostrano che l’espressione di GAT-1 nelle sinapsi
GABAergiche è all’incirca nel 60% dei casi nei terminali, nel 29% nei soli astrociti
perisinaptici e nell’11% in entrambi i comparti. Mentre nel caso di GAT-3 è nel 78%
negli astrociti perisinaptici, 13% nei terminali e 8% in entrambi. Inoltre nei terminali
assonici, GAT-1 è distribuito nell’area peri-sinaptica ed extrasinaptica, mentre nei
processi astrocitari è presente maggiormente nella zona extrasinaptica. Per quanto
2
riguarda GAT-3, nei processi astrocitari è maggiormente concentrato nell’area
extrasinaptica, mentre nei terminali è sparso, senza formare un vero e proprio
agglomerato.
Infine, i livelli di GAT-1 e GAT-3 nelle sinapsi GABAergicche sono stati
stimati attraverso microscopia confocale-3D ad alta risoluzione applicata ai terminali
VGAT: a livello delle sinapsi GABAergiche, GAT-1 è significativamente più espresso
(~1,5 volte) rispetto a GAT-3.
In conclusione, i risultati sull’espressione e sulla fine localizzazione di GAT-1 e
GAT-3 nelle sinapsi GABAergiche, consentono da un lato di elucidare il ruolo dei due
trasportatori nella regolazione dei fenomeni sia fasici che tonici del GABA e dall'altro
di suggerire la possibilità di un dualismo funzionale di GAT-1 (determinato dalla
regolazione dei livelli di GABA nei siti sinaptici ed extrasinaptici), mentre GAT-3
mostrerebbe una singola attività funzionale (regolazione dei livelli di GABA nei siti
extrasinaptici)
A quantitative analysis of cellular and synaptic localization of GAT-1 and GAT-3 in rat neocortex
A role for GAT-1 in Presynaptic GABA Homeostasis?
In monoamine-releasing terminals, neurotransmitter transporters – in addition to terminating synaptic transmission by clearing released transmitters from the extracellular space - are the primary mechanism for replenishing transmitter stores and thus regulate presynaptic homeostasis. Here, we analyze whether GAT-1, the main plasma membrane GABA transporter, plays a similar role in GABAergic terminals. Re-examination of existing literature and recent data gathered in our laboratory show that GABA homeostasis in GABAergic terminals is dominated by the activity of the GABA synthesizing enzyme and that GAT-1-mediated GABA transport contributes to cytosolic GABA levels. However, analysis of GAT-1 KO, besides demonstrating the effects of reduced clearance, reveals the existence of changes compatible with an impaired presynaptic function, as mIPSCs frequency is reduced by one third and GADs and PAG levels are significantly up-regulated. Although the changes observed are less robust than those reported in mice with impaired dopamine, noradrenaline and serotonin plasma membrane transporters, they suggest that in GABAergic terminals GAT-1 impacts on presynaptic GABA homeostasis, and may contribute to the activity-dependent regulation of in
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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